PROJECT SUMMARY/ABSTRACT Exposure assessment is necessary for evaluating the health effects of tobacco use. Measuring exposure to toxic and addictive substances is important for achieving the integrative theme of this TCORS, that understanding combined health effects, behavior, and impact analysis will provide actionable information for regulation of and public communications about current and emerging tobacco products The Biomarker Core will contribute to this goal through three specific aims: (1) Provide analytical chemistry support for UCSF TCORS investigators; (2) Continue and expand cross-TCORS collaborations by making available state-of-the- art analytical methods to foster such collaborations; (3) Develop new biomarkers of exposure to tobacco products. The Biomarker Core will identify new biomarkers of exposure and potential harm for new and emerging tobacco products, in particular e-cigarettes and heat-not-burn (HNB) products. The Biomarker Core will support studies carried out by TCORS investigators by analysis of biofluid samples for biomarkers of exposure and potential harm (Projects 1-4), and by analyzing tobacco products (e-cigarettes and HNB products) and their aerosols (Projects 1-3) for harmful and potentially harmful chemicals (HPHCs). Dr. Jacob and his senior laboratory staff have more than 30 years' experience in supporting large-scale studies and developing new biomarkers and analytical methods. The Biomarker Core laboratory will measure tobacco alkaloids and a wide range of toxic substances and other components of interest in both products and their aerosols. The core will assist the investigators of Projects 1, 2, and 3 in implementing protocols that will generate aerosols for chemical analysis and for delivery to in vitro systems and animals for toxicology studies. The analytical methods employed by the Biomarker Core are mostly chromatographic?mass spectrometric (GC-MS and LC-MS/MS) performed on triple quadrupole mass spectrometers, generally considered the gold standard for quantitative analysis of complex biological samples. As in our current TCORS, the Biomarker Core also expects to use its methods in collaborations with other TCORS beyond UCSF. Providing state-of-the-art exposure assessment to the individual projects, developing improved exposure assessment measures, and identifying substances in new and emerging tobacco products and their aerosols that lead to toxic substance exposure could contribute to the development of product standards for potential reduced risk products, as well as advance the field of tobacco exposure assessment in general.